[1281] Immunohistochemical Profiling of Primary Mediastinal Lymphomas

ME Arcila, J Teruja-Feldstein. Memorial Sloan Kettering Cancer Center, New York

Background: Primary mediastinal large B cell lymphoma (PMBCL) is a subtype of diffuse large B cell lymphoma (DLBCL) characterized by specific clinical, molecular and genetic features. Despite its unique attributes, overlapping features with other lymphomas involving the mediastinum can present a diagnostic challenge. Recently, a number of protein markers distinguishing PMBCL from other DLBCLs and classical Hodgkin lymphoma (cHL) have been proposed including TRAF1, c-REL, c-Jun and Gal1. When used in combination, these could serve as diagnostic biomarkers that help delineate these entities. Herein we describe our validation testing of these markers for routine immunohistochemical profiling of lymphomas of the mediastinum.
Design: Paraffin embedded tissue blocks were obtained from 41 patients with PMLBCL, 63 with other DLBC and 48 cHL. Tumor samples were prepared in tissue microarrays with triplicate cores on each sample and stained by immunohistochemistry with antibodies against TRAF1, c-REL, c-Jun and Gal1. The pattern of expression was then graded for each tumor based on intensity of cytoplasmic and/or nuclear staining and was analyzed with relation to the clinicopathologic data. (Evaluation of CD20 positive cHL and grey zone lymphomas is in progress).
Results: Expression profiles for all markers summarized in table 1. (Denominator = number of evaluable samples). Sensitivity & specificity sumarized in table 2.

Expression of Gal-1, c-Jun, TRAF and c-REL in DLBCL, MLBCL and cHL

	PMBCL	DLBCL	cHL
TRAF	63% (26/41)	8% (5/62)	98% (46/47)
c-REL	59% (23/41)	9.6% (6/62)	83%(24/29)
GAL1	21% (9/42)	9.5% (6/63)	97% (35/36 )
c-JUN	0% (0/41)	3% (2/63)	97% (31/32)
TRAF + & c-REL+	39% (16/41)	1.6% (1/62)	83% (24/29)
GAL + & c-JUN+	0% (0/41)	3%(2/63)	97% (31/32)

TABLE 2. Sensitivity and Specificity of c-Rel , TRAF1, Gal1 and c-Jun for PMBCL and cHL

	Sensitivity (%)	Specificity (%)
PMBCL versus other DLBCLs
cRel +	59%	90%
TRAF1+	63%	92%
c-Rel + &TRAF1	39%	98%
cHL versus other DLBCLs
GAL1	85%	86%
c-JUN	88%	97%
GAL + & c-JUN+	90%	97%

Conclusions: The combined expression of c-Rel and TRAF is a highly specific (98%) and moderately sensitive (39%), way to distinguish PMBCL from DLBCL but not from cHL. The combined presence of GAL1 and c-Jun is highly sensitive (90%) and specific (98%) for cHL, further delineating the boundaries between these 3 entities. This panel can be readily applied to the routine IHC evaluation of large cell lymphomas of the mediastinum and may be a useful adjunct in the profiling of difficult cases.
Category: Hematopathology

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 176, Monday Morning